CN116509859A - Use of lansoprazole for improving metabolism and treating obesity - Google Patents

Abstract

The present invention relates to the use of lansoprazole for enhancing metabolism and treating obesity. In particular to various applications of lansoprazole in reducing the content of visceral white fat in a subject, improving the brown fat content, increasing the insulin sensitivity of the subject, reducing insulin resistance, improving the metabolic rate of the subject, treating type II diabetes, fatty liver, cardiovascular and cerebrovascular diseases, gall bladder diseases, sleep disorders or cancers caused by obesity and the like. The invention discovers the application of lansoprazole in metabolism for the first time, and proves that the lansoprazole can reduce the weight, visceral fat content and fat volume of a high-fat diet subject on the premise of not influencing appetite, improve the brown fat proportion of the subject and improve the insulin sensitivity of the subject. The experimental result of the invention expands the application field of lansoprazole, and is expected to become a medicine for losing weight, improving metabolism and improving insulin sensitivity of a subject.

Description

Application of Lansoprazole in Improving Metabolism and Treating Obesity

Technical field:

The invention belongs to the field of biomedicine, and particularly relates to the application of lansoprazole in improving metabolism, reducing insulin resistance and treating obesity.

Background technique

With rapid urbanization and economic development, the obesity rate worldwide is increasing year by year, and the incidence of obesity-related metabolic diseases (such as type 2 diabetes, fatty liver, and hypertension) continues to rise. Therefore, effective control of weight gain or improvement of obesity is particularly important for the prevention and treatment of chronic metabolic diseases. Brown adipose tissue (brown adipose tissue) and beige adipose tissue (beige adipose tissue) can be activated to generate heat through non-shivering thermogenic energy consumption, thereby improving energy metabolism and treating obesity and related chronic metabolic diseases.

At present, lansoprazole is mainly used for the treatment of gastric ulcer, duodenal ulcer, and reflux esophagitis, but there is no published literature on lansoprazole having a weight loss effect.

Contents of the invention

In order to solve the problems in the prior art, the present invention provides the use of lansoprazole in activating brown fat, reducing the fat content of subjects and improving insulin sensitivity.

One aspect of the present invention provides the use of lansoprazole in the preparation of a medicament for reducing the white fat content and/or increasing the brown fat content of a subject.

Further, the white fat is white visceral fat.

Further, the subject is obese due to overeating or high-fat diet.

Another aspect of the present invention provides the use of lansoprazole in the preparation of a drug for improving insulin sensitivity and/or improving insulin resistance of a subject.

Further, the subject is an obese subject due to overeating or high-fat diet.

Further, said improving insulin sensitivity is improving glucose tolerance and/or improving insulin tolerance.

Yet another aspect of the present invention provides the use of lansoprazole in the preparation of a drug for increasing catabolic stored energy of a subject.

Another aspect of the present invention provides the use of lansoprazole in the preparation of medicines for treating chronic metabolic diseases.

Further, the chronic metabolic disease is selected from type II diabetes caused by obesity, fatty liver, cardiovascular and cerebrovascular diseases, gallbladder diseases, sleep disorders or cancer.

Another aspect of the present invention provides the use of lansoprazole in the preparation of agonists of the thermogenesis-related genes UCP-1, PRDM-16 or DIO2 in brown fat.

Another aspect of the present invention provides the use of lansoprazole in the preparation of medicines for treating obesity and promoting weight loss.

Another aspect of the present invention provides a pharmaceutical composition for improving insulin sensitivity of a subject or reducing fat content of a subject, wherein lansoprazole is used as an active ingredient in the pharmaceutical composition.

Another aspect of the present invention provides a method for reducing fat content of a subject, treating obesity, and promoting weight loss, the method comprising administering an effective amount of lansoprazole to the subject.

Still another aspect of the present invention provides a method for increasing the energy stored by catabolic metabolism of the subject, improving the insulin sensitivity of the subject or increasing the brown fat ratio of the subject, the method comprising administering to the subject an effective amount of Lansol Larazole.

Beneficial effect: compared with the prior art, the present invention has the following remarkable features:

The present invention first discovers the use of lansoprazole in metabolism, and proves that lansoprazole can reduce the body weight, visceral fat content and fat volume of subjects on a high-fat diet without affecting appetite, and increase the body weight of subjects on a high-fat diet. Increase the proportion of brown fat, improve the insulin sensitivity of the subjects, increase the expression of gene production and improve metabolic efficiency. The experimental result of the present invention expands the application field of lansoprazole, and is expected to become a medicine for losing weight, improving metabolism and improving insulin sensitivity of subjects.

Description of drawings

Fig. 1 is that the body weight of high-fat diet (HFD) feeds mouse vehicle group and lansoprazole administration group changes with administration time.

Fig. 2 is the body weight change percentage after administration of HFD mice vehicle group and lansoprazole administration group.

Fig. 3 is the food intake of HFD feeding mice vehicle group and lansoprazole administration group.

Figure 4 is the percentage by weight of brown fat, inguinal subcutaneous fat, and epididymal fat after administration of HFD-induced obese mice.

Fig. 5 is the fat volume of CT measurement solvent group and lansoprazole administration group, bone volume comparison.

Fig. 6 is the glucose tolerance test (GTT) of solvent group and lansoprazole administration group.

Fig. 7 is the insulin tolerance test (ITT) of solvent group and lansoprazole administration group.

Figure 8 shows the expression of genes related to heat production in brown adipose tissue of mice in the solvent group and the lansoprazole administration group in the high-fat diet model.

Detailed ways

The present invention will be further described below in conjunction with embodiment, but should not limit protection scope of the present invention with this.

"Treating" means alleviating, in whole or in part, the symptoms associated with a condition or disorder (eg, a disease), or stopping the further progression or worsening of these symptoms, or preventing or prophylaxis of the disease or disorder. Likewise, as used in this article,

"Effective amount" refers to the amount of a compound that will relieve all or part of the symptoms associated with a condition or disorder, or stop the further progression or worsening of these symptoms, or prevent or provide prophylaxis against said disease or disorder . For example, in the treatment of obesity, an example of a desired therapeutic outcome is a slowing or cessation of weight gain, or a decrease in body weight.

The materials in the examples are all commercially available products, C57BL/6J mice, male, 8 weeks, 20-22g, purchased from Huafukang Company; high-fat feed: purchased from MP Company, 60% kcal high-fat feed 0296044910 -i; All animal experiments were strictly in accordance with the requirements of the "Guidelines for the Management and Use of Experimental Animals" and were approved by the Experimental Animal Management Committee of Capital Medical University. Lansoprazole was purchased from Yuanye Biological Co., Ltd., CAS 103577-45-3, molecular formula: C16H14F3N3O2S, white solid, average molecular weight 369.36.

In the present invention, when C57BL/6J mice are administered, the administration group is to give mice the lansoprazole solution dissolved in 2.5% DMSO/normal saline; the solvent (Vehicle) group is to give mice 2.5% DMSO/normal saline .

Obesity model test of embodiment 1 high-fat diet

The wild-type mice were fed with high-fat diet (60% kcal high-fat diet) for 10 weeks, and the body weight and food intake of the mice were monitored. After 10 weeks of high-fat diet, the average body weight of the mice increased to more than 30 g, forming a high-fat diet obesity model for mice. The mice that high-fat diet induces obesity are divided into two groups at random, respectively continuous subcutaneous injection solvent (2.5%DMSO/normal saline, Vehicle group) or lansoprazole (lansoprazole solution dissolved in 2.5%DMSO/normal saline , administration group LPZ), continued to give the mice a high-fat diet, and monitored the body weight and food intake of the mice.

After 3 weeks of continuous subcutaneous injection, insulin sensitivity test, including glucose tolerance test and insulin tolerance test, see Example 2. CT analysis was performed at 5 weeks after administration, and mouse tissues were collected at the end. At the same time, brown fat (BAT), inguinal subcutaneous fat (iWAT) and white epididymal fat (eWAT) were collected, weighed, and the weight percentage of each fat tissue was counted.

The test results are shown in Figures 1, 2 and 3. Figure 1 shows the changes in body weight of mice over time from 0 to 15 weeks, and the administration time point is 11 to 15 weeks. During the first 10 weeks, the mice continued to gain weight due to the continuous intake of a high-fat diet. After administration, the body weight change trend of the mice in the solvent group remained unchanged, while the weight gain of the mice in the administration group slowed down. Figure 2 shows the change in the percentage of body weight of the mice in the 10th to 13th weeks after administration over time. It can be seen that the weight change trend of the mice in the solvent group and the administration group is significantly different. In the solvent group, the body weight of the mice increases by 20%, while the body weight of the mice in the administration group only increases by less than 5%. The observation of the feed intake during the drug administration showed that the feed intake of the mice did not increase or decrease due to the injection of the drug (Figure 3). In summary, after 3 weeks of administration of lansoprazole, the weight gain of mice in the lansoprazole group decreased significantly compared to the solvent group, and there was no difference in food intake, indicating that lansoprazole can reduce the weight gain caused by a high-fat diet .

The brown fat (BAT), inguinal subcutaneous fat (iWAT) and white epididymal fat (eWAT) weight results of two groups of mice after administration are shown in Figure 4, and the brown fat weight percentage of lansoprazole administration group is higher than solvent group, There are significant differences. The weight percentage of visceral fat was lower than that of the solvent group, and there was a significant difference. There was no difference in the weight percentage of subcutaneous fat between the two groups. The experimental results show that the effect of lansoprazole on fat is mainly reflected in increasing the proportion of brown fat and reducing the proportion of visceral fat, but has little effect on subcutaneous fat.

The results of the body composition analysis of the mice are shown in Figure 5, and Figure 5 shows the comparison of fat volume and bone volume in the solvent group and the lansoprazole-administered group by CT respectively. The CT data showed that the fat volume of the lansoprazole administration group was significantly smaller than that of the solvent group, and there was a significant difference, but there was no difference in the bone volume between the two groups, indicating that the main reason for the weight loss of the mice in the lansoprazole administration group was that the fat content decreased .

Embodiment 2 insulin sensitivity test

Glucose tolerance test (Glucose tolerance test): Vehicle group and lansoprazole administration group mice are fasted 16h after taking blood to measure initial blood glucose value (0 time point) through tail vein, intraperitoneal injection of glucose (2g/kg) after each Blood was taken from the tail vein at 0.5h to measure the blood glucose level. A total of 2h was measured.

Insulin tolerance test (Insulin tolerance test): After fasting for 4 hours in the Vehicle group and the lansoprazole-administered group, blood was taken from the tail vein to measure the initial blood glucose value (0 time point), and after intraperitoneal injection of insulin (0.5U/kg) Blood was taken from the tail vein every 0.5 h to determine the blood glucose level. A total of 2h was measured.

The results of the glucose tolerance test are shown in Figure 6. The blood glucose concentration of the lansoprazole administration group decreased rapidly compared with the solvent group, and there was a statistical difference between the two. The results of the insulin tolerance test are shown in Figure 7. The blood glucose concentration of the lansoprazole administration group decreased rapidly compared with the solvent group. Is there a statistical difference between the two? Glucose tolerance test and insulin tolerance test show that lansoprazole can improve insulin sensitivity and insulin resistance in mice.

Example 3 Research on genes related to brown fat thermogenesis

The brown fat of the mice in the administration group and the solvent group of Examples 1 and 2 was taken to study the changes in mRNA expression of genes related to brown fat thermogenesis. Tissue RNA was extracted by Trizol method and reverse-transcribed into cDNA, and the expression level of genes related to brown fat thermogenesis (UCP-1, PRDM-16, DIO2) was measured by qPCR instrument, GAPDH was used as an internal reference gene, and 2 ^-ΔΔCt normalization method Statistical data.

The qPCR results are shown in Figure 8. The results showed that compared with the solvent group, the expression of thermogenesis-related genes UCP-1, PRDM-16 and DIO2 in the brown fat of the lansoprazole-administered group was up-regulated. It shows that lansoprazole may regulate energy metabolism and insulin sensitivity by up-regulating thermogenesis-related genes in brown fat.

The above-mentioned embodiments are part of the implementation of the present invention, but the implementation of the present invention is not limited by the above-mentioned examples, and any other changes, modifications, substitutions, combinations, and simplifications that do not deviate from the spirit and principles of the present invention , all should be equivalent replacement methods, and are all included in the protection scope of the present invention.

Claims (10)

1. The purposes of lansoprazole in the preparation reducing the medicine of experimenter's white fat content; Preferably, the white fat is white visceral fat. 2. Lansoprazole is used in the preparation of the medicine that increases experimenter's brown fat content. 3. The purposes of lansoprazole in the preparation of improving the insulin sensitivity of experimenter and or improving the medicine of insulin resistance; Preferably, said improving insulin sensitivity is improving glucose tolerance and or improving insulin tolerance. 4. The use of lansoprazole in the preparation of a medicament for improving the energy stored by catabolism of a subject. 5. Lansoprazole is used in the preparation of the medicine for the treatment of chronic metabolic diseases; Preferably, the chronic metabolic disease is selected from type II diabetes caused by obesity, fatty liver, cardiovascular and cerebrovascular diseases, gallbladder disease, sleep disorders or cancer. 6. The use of lansoprazole in the preparation of agonists of thermogenesis-related genes Ucp-1, Prdm-16 or DIO2 in brown fat. 7. Lansoprazole is used in the preparation of the medicine for treating obesity and promoting weight loss. 8. A pharmaceutical composition for improving insulin sensitivity of a subject or reducing fat content of a subject, using lansoprazole as an active ingredient in the pharmaceutical composition. 9. A method for reducing fat content in a subject, treating obesity, and promoting weight loss, said method comprising giving the subject an effective dose of lansoprazole; Preferably, the subject is an obese subject due to overeating or a high-fat diet. 10. A method for improving the energy stored by catabolism of the experimenter, improving the insulin sensitivity of the experimenter or improving the brown fat ratio of the experimenter, said method comprising giving the experimenter an effective dose of lansoprazole; Preferably, the subject is an obese subject due to overeating or a high-fat diet.